This is an application for competitive renewal of an R01 whose focus is the detection of myocardial viability and infarction by contrast-enhanced MRI. The past four years of funding have supported a series of basic science studies focused primarily on the relationship of "delayed hyperenhancement" to myocardial necrosis and scar. These studies formed the basis for clinical studies of "delayed enhancement" which demonstrated the technique can be used to predict recovery of contractile function following revascularization and that it can be used to detect subendocardial human infarcts which are routinely missed by existing diagnostic techniques. On the basis of our work and that of other groups, the "delayed enhancement" technique is now being used at growing number of medical institutions and was recently recognized in a survey by the Society of Cardiovascular Magnetic Resonance as "the most important clinical application of cardiovascular magnetic resonance" (see Figure 1). Despite these successes, however, recent data also demonstrate that the "delayed enhancement" technique can underestimate or overestimate the true spatial extent of myocardial viability and infarction depending on how the imaging protocol is performed (see Figure 2). This issue limits widespread use of the technique for clinical diagnosis, limits its use as an end-point for multicenter clinical trials, and limits its use as a tool for the study of new physiology. In Specific Aim 1 we propose to establish how in vivo measurements of the transmural extent of infarction and total infarct size are affected by the imaging protocol and, by comparison to the "gold standard" of histologic examination, to define guidelines which can be used to assure accurate, reproducible measurements at multiple institutions using the "traditional" segmented IR-FLASH pulse sequence. In Specific Aim 2 we propose to develop entirely new MRI pulse sequences which, as demonstrated in our "Preliminary Studies", address clinically-relevant limitations of segmented IR-FLASH. We then propose (Aim 3) to test the hypothesis that the standardized techniques established by Aims 1 and 2 can be used to better define myocardial infarct size than any existing technique. If this hypothesis proves correct, the use of MRI "delayed enhancement" as the end-point for clinical trials will significantly reduce the number of patients needed to evaluate new therapies. The overall goal of these studies is to establish the foundation for widespread use of the "delayed enhancement" technique for both routine clinical diagnosis and multi-center clinical investigation.